Proteomic Insights into Intrauterine Growth Restriction and Its Role in Asthma Pathogenesis

Intrauterine growth restriction (IUGR) increases risk of developing respiratory diseases such as asthma later in life. This study aims to characterize the effects of maternal hypoxia-induced IUGR on the lung proteome and identify key altered pathways relevant to asthma development in male and female adult offspring. Pregnant mice were housed in hypoxic conditions (10.5% oxygen) from gestational day 11 to 17.5 and returned to normoxic conditions until term (gestational day ∼21). Control animals were housed in normoxic conditions throughout pregnancy. Offspring were weighed at birth. At 8 weeks, mice were weighed and right lung tissues collected for analysis. Proteomics profiling was performed using liquid chromatography tandem mass spectrometry to identify and quantify individual proteins. Mass spectrometry identified 1417 proteins with significant differences (Benjamini-Hochberg corrected p < 0.05) between IUGR and control mice. IUGR mice showed reduced mitochondrial respiration complex proteins which may cause increased oxidative stress, compared to Controls. Many ribosomal subunit proteins were decreased, which may impact protein translation. Store-operated calcium entry proteins were increased in IUGR mice, indicating calcium homeostasis dysregulation. IUGR mediated protein expression changes in the lungs may alter key cellular processes. In-depth characterization of these changes can further elucidate disease pathways between IUGR and asthma.